Field Effect

由 sufang 在 二, 07/29/2014 - 23:14 發表 Pre-published Field Effect NOTCH Oral Cancer

重要文獻:

1. Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11: 9-22. (pdf 2833)
2. Hu B, Castillo E, Harewood L, Ostano P, Reymond A, et al. (2012) Multifocal Epithelial Tumors and Field Cancerization from Loss of Mesenchymal CSL Signaling. Cell 149: 1207-1220. (PubMed) (pdf 3435)
3. Vanharanta S, Massague J (2012) Field cancerization: something new under the sun. Cell 149: 1179-1181. (PubMed) (pdf 3438)
4. Troester M (2012) Genomic Characterization of Cancer-Adjacent Tissue: Evidence of Field Effects and Expression Subtypes. TCGA Second Annual Scientific Symposium. (pdf 3938)
5. Alcolea MP, Greulich P, Wabik A, Frede J, Simons BD, et al. (2014) Differentiation imbalance in single oesophageal progenitor cells causes clonal immortalization and field change. Nat Cell Biol 10.1038/ncb2963. (Ingrid Journal Club Paper) (PubMed) (pdf 4024)
6. Frede J, Adams DJ, Jones PH (2014) Mutation, clonal fitness and field change in epithelial carcinogenesis. J Pathol 10.1002/path.4409. (pdf 4133)

J Pathol. 2014 Jul 21. doi: 10.1002/path.4409. [Epub ahead of print]

Mutation, clonal fitness and field change in epithelial carcinogenesis. (pdf 4133)

Frede J¹, Adams DJ, Jones PH.

Author information

Abstract

Developments in lineage tracing in mouse models have revealed how stem cells maintain normal squamous and glandular epithelia. Here we review recent quantitative studies tracing the fate of individual mutant stem cells which have uncovered how common oncogenic mutations alter cell behaviour, creating clones with a growth advantage that may persist long term. In the intestine this occurs by a mutant clone colonizing an entire crypt, whilst in the squamous oesophagus blocking differentiation creates clones that expand to colonize large areas of epithelium, a phenomenon known as field change. We consider the implications of these findings for early cancer evolution and the cancer stem cell hypothesis, and the prospects of targeted cancer prevention by purging mutant clones from normal appearing epithelia.

重要文獻列表_Cholangiocarcinoma

FGFR2 Gene Fusion文獻快速入門:

1    Wu, Y. M., F. Su, S. Kalyana-Sundaram, N. Khazanov, B. Ateeq, X. Cao, R. J. Lonigro, P. Vats, R. Wang, S. F. Lin, A. J. Cheng, L. P. Kunju, J. Siddiqui, S. A. Tomlins, P. Wyngaard, S. Sadis, S. Roychowdhury, M. H. Hussain, F. Y. Feng, M. M. Zalupski, M. Talpaz, K. J. Pienta, D. R. Rhodes, D. R. Robinson, and A. M. Chinnaiyan. Identification of targetable FGFR gene fusions in diverse cancers. (2013). Cancer discovery. 3: 636-47. 

2    Arai, Y., Y. Totoki, F. Hosoda, T. Shirota, N. Hama, H. Nakamura, H. Ojima, K. Furuta, K. Shimada, T. Okusaka, A. Kosuge, and T. Shibata. FGFR2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. (2014). Hepatology. 59, 1427-34.

3    Ross, J. S., K. Wang, L. Gay, R. Al-Rohil, J. V. Rand, D. M. Jones, H. J. Lee, C. E. Sheehan, G. A. Otto, G. Palmer, R. Yelensky, D. Lipson, D. Morosini, M. Hawryluk, D. V. Catenacci, V. A. Miller, C. Churi, S. Ali, and P. J. Stephens. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. (2014). Oncologist. 19: 235-42. 

4    Borad, M. J., M. D. Champion, J. B. Egan, W. S. Liang, R. Fonseca, A. H. Bryce, A. E. McCullough, M. T. Barrett, K. Hunt, M. D. Patel, S. W. Young, J. M. Collins, A. C. Silva, R. M. Condjella, M. Block, R. R. McWilliams, K. N. Lazaridis, E. W. Klee, K. C. Bible, P. Harris, G. R. Oliver, J. D. Bhavsar, A. A. Nair, S. Middha, Y. Asmann, J. P. Kocher, K. Schahl, B. R. Kipp, E. G. Barr Fritcher, A. Baker, J. Aldrich, A. Kurdoglu, T. Izatt, A. Christoforides, I. Cherni, S. Nasser, R. Reiman, L. Phillips, J. McDonald, J. Adkins, S. D. Mastrian, P. Placek, A. T. Watanabe, J. Lobello, H. Han, D. Von Hoff, D. W. Craig, A. K. Stewart, and J. D. Carpten. (2014) (Mayo Clinic Cancer Center, Arizon and Mayo Clinic, Minnesota) Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma. . PLoS Genet. 10: e1004135. 

5    Graham, R. P., E. G. Barr Fritcher, E. Pestova, J. Schulz, L. A. Sitailo, G. Vasmatzis, S. J. Murphy, R. R. McWilliams, S. N. Hart, K. C. Halling, L. R. Roberts, G. J. Gores, F. J. Couch, L. Zhang, M. J. Borad, and B. R. Kipp. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. (2014). Human pathology. 45: 1630-8.

6   Sia D, Losic B, Moeini A, Cabellos L, Hao K, et al. (2015) Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma. Nat Commun 6: 6087.

7   Shaw AT, Hsu, PP, Awad, MM & Engelman, JA. Tyrosine kinase gene rearrangements in epithelial malignancies. Nat Rev Cancer 2013; 13, 772-787.

8   Zheng Z, Liebers M, Zhelyazkova B, Cao Y, Panditi D, et al. (2014) Anchored multiplex PCR for targeted next-generation sequencing. Nat Med 20: 1479-1484.

9.  Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, et al. (2014) The landscape and therapeutic relevance of cancer-associated transcript fusions. Oncogene 10.1038/onc.2014.406.

10  Klijn C, Durinck S, Stawiski EW, Haverty PM, Jiang Z, et al. (2015) A comprehensive transcriptional portrait of human cancer cell lines. Nat Biotechnol 33: 306-312.

NHRI TLCN CCA 檢體申請書

由 sufang 在 五, 07/25/2014 - 10:50 發表 Pre-published CCA TLCN申請書 檢體

Letter_of_Intent_FGFR fusion (to be FTPd)

Biosamples_Request_Form_gene fusion (to be FTPd)

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相關書信  a recent published genomic changes in IHCC 12 messages
LTCHEN Sun, Mar 23, 2014 at 9:55 AM To: hung1228 , "Kelvin Tsai K." , Chien-Feng Li , Su-Fang Lin , 姜乃榕 , Chiun Hsu
Cc: LTCHEN Dear ALL:
A recent published genomic changes in IHCC for your reference, including IDH 1/2 mutation and FGFR2 fusion!
Best egards, LT Chen IHCC genomic changes Oncoloist'14.pdf 1372K  Su-Fang Lin To: LTCHEN Cc: hung1228 , "Kelvin Tsai K." , Chien-Feng Li , 姜乃榕 , Chiun Hsu
This is really neat!! Are there accompanying supplemental materials associated with this communication? (I am curious about what are the 182 cancer genes and the 36 introns). Also, is that a routine to use various IHC stainings in ruling out non hepatic primary tumors including NSLSCL, breast cancer, prostate cancer, neuroendocrine carcinoma?) In other words, is that a common feature that other cancer types frequently metastasize to this site?
Thanks for the answers in advance!! Su-Fang

Dear SF:
usually the possibility of secondary liver tumors were excluded by history and clinical imaging study! Best LTC

Dear DY:
Enclosed, some papers for your reference! We are interested in some fusion genes in IHCC, including the FGFR2, ROS-1 and ALK! Can you help to design some RT-PCR methods to detect these mutations, we can try to have some RNA from fresh frozen and formalin fixed paraffin embedded tissues for testing in parallel! If possible, will you come to visit out institute in Tainan at W3 morning, perhaps around 10:00am (you can take the 9:00 am 自強 from kaohsiung to Tainan, it will arrive around 9:30-35, then you can take a shuttle that will leave the Tainan rear station 後火車站 at 9:40 to NCKUH! or please just call me to let you know your departure time and I shall pick you up at the rear Tainan station! Best LT Chen

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Su-Fang Lin Mon, Mar 24, 2014 at 10:09 AM To: LTCHEN , Daw-yang Hwang 黃道揚 <910208 mail.kmuh.org.tw="">
Cc: "Kelvin K. Tsai" , hung1228 , Pon
Dear 所長: 我星期三這裡有meeting,所以就不過去「熱烈歡迎」黃醫師囉!
但是先跟大家報告⼀下上星期我與UMich Dr. Dan Robinson (@Chinnaiyan Lab)討論過、 我們的60個膽道癌檢體想要請他們幫忙做RNA-seq, 要找gene fusion. 他again,爽快地說可 以當做research cohort,就把檢體送過去,當他們臨床loading較輕時,會幫我們的檢體放 進去、⼀批一批做出來。Novartis clinical trial那部份, 那他們就會要廠商支付耗材費、目 前與他們合作的廠商是pay他們約5000美金/sample (MI-ONCOSEQ). (Novartis is not one of them, he guessed the PET result we saw last time could be the one sent to Detroit, where Novartis has a big cohort for their clinical trial on FGFR inhibitors)
黃醫師在哈佛的mentor, Dr Hildebrandt, 是不是在UMich還有Lab? 您說暑假會去(UMich) 那裡visit個2–3週,是可以做實驗的嗎? 還是補paper or family trip? Dan Robinson也是龔 行健院長的學生, 他在CWRU的成名作就是以multi-plex PCR檢查cancer cell中90個 protein tyrosine kinase的表現情形。他NGS的library做得非常好,用眼睛找fusion gene的 功力更是沒話說,若能和他聊⼀一聊應該會收獲很多(不過,他們NGS做慣了,可能會要你 打消主意只用PCR看少數gene fusion...) Best, Su-Fang (菩薩保佑台灣!)

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Su-Fang Lin To: 陳所長   Tue, Mar 25, 2014 at 4:51 PM
Dear 所長:
初稿寫好了, 有空可以麻煩您不吝斧正一下嗎? 感謝~
Best, Su-Fang

2 attachments
Letter_of_Intent_FGFR fusion.doc 76K
Biosamples_Request_Form_gene fusion.doc 44K

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Daw-yang Hwang 黃道揚 <910208 mail.kmuh.org.tw="">
Wed, Mar 26, 2014 at 9:32 PM
To: Su-Fang Lin , LTCHEN , Daw-yang Hwang 黃道揚 <910208 mail.kmuh.org.tw="">
Cc: "Kelvin K. Tsai" , hung1228 , Pon
Dear all,
It is very nice to visit NHRI in Tainan, enjoy a good lunch, and meet and discuss collaborations in the future. Please let me know if I can be of any help! I will find out the computer system and software (CLCbio Workbench) quote, and will work on the bisulfite analysis.

5 of 9 4/8/14 9:13 AM
Gmail - a recent published genomic changes in IHCC https://mail.google.com/mail/u/0/?ui=2&ik=d85e4...

 

Dr. Hildebrandt dose not have a lab in UMich anymore. I will go there to visit a collaborator, and also for a family trip. I will be very happy if I can visit Dr. Robinson, if Dr. SF Lin can to introduce me to him. I was very aware of his previous tyrosine kinase work when I was student.
I will order a Illumina library preparation kit to test our fusion gene hypothesis, the Illumina sales is out of town these few days. Hope our concept can work.
Kindly regards, Daw-yang

Start: 07/25/2014

5年前的一個小實驗 (EBV and KSHV Methylation)

由 natsumi 在 四, 07/17/2014 - 17:30 發表 EBV and KSHV Methylation

最近聽Dr. Lin講Methylation的故事，我想到之前曾經做過的一個小實驗，分享之。

AB851

CellProfiler

Paper:
http://genomebiology.com/content/pdf/gb-2006-7-10-r100.pdf

軟體下載網頁:
http://www.cellprofiler.org/

這也是BROAD Institute 出的一個軟體

應該可以取代AIS 來計算invasion 細胞數目

甚至可以提供更多功能

只是 目前我自己沒有要用到的地方 就沒有鑽研了!

缺口計畫相關資訊

由 sufang 在 六, 07/05/2014 - 17:12 發表 Pre-published Arecoline COE (Cancer of Excellence) OPMD Potentially malignant disorder

10/05/2014 (SUN) PK大賽

第二期癌症研究缺口補強計畫評選會議議程

開會時間：103年10月5日（星期日）上午10時

開會地點：本部204會議室

壹、主席致詞

貳、報告